The proposed research is directed at designing and demonstrating a compact, cost-effective high-frequency, tunable 2nd-harmonic gyrotron for Dynamic Nuclear Polarization (DNP) enhanced solid-state Nuclear Magnetic Resonance (SSNMR) spectroscopy at 600 MHz. With DNP, the inherently small signal intensities in a NMR experiment can be enhanced by several orders of magnitude. This significantly increased overall sensitivity will be of great value for the structural characterization of proteins, peptides, or micro RNAs that normally exist in complex biologically-relevant mixtures at concentrations beyond the sensitivity of conventional NMR. In the last decade, this technique has proven to be a robust method to increase signal intensities in NMR in laboratories around the world, making a modular, compact, cost-effective gyrotron-based DNP system well-timed for commercial deployment. The successful development of this system will enable the rapid proliferation of DNP enhanced NMR for structural biology, pharmaceutical research and material science, which are of interest in many projects funded by the U.S. National Institutes of Health. DNP requires a continuous-wave (CW), high-power (>20W), high-frequency terahertz source such as a gyrotron to transfer the high thermal polarization of the electron to the surrounding nuclei. In phase I we propose to develop a 395 GHz, 20 W 2nd harmonic gyrotron with 1GHz tuning range that will benefit from a standard wide-bore (89 mm) superconducting magnet, a significant cost-reduction for the gyrotron and thus the overall system. The gyrotron will operate at 395 GHz, however, the technology will be applicable for the full range of wide-bore (89 mm) spectrometers available for biosolids, from 300 MHz to 800 MHz. The system will be interfaced to a cryogenic Magic Angle Spinning SSNMR probe curently under development at Varian Incorporated, alowing us to demonstrate a functional DNP system by the end of Phase I. We expect signal enhancement of >250, corresponding to a time reduction for signal acquisition of >60,000. The system will have several novel features that will allow customers to simply upgrade their existing NMR systems, thus conserving their investment in existing instruments. The large tunability (>1 GHz) will enable researchers to use a broad range of currently available polarizing agents, as well as develop new ones without the need for a sweep coil to change the field of the NMR magnet. In phase II of the project we will further evaluate the overall gyrotron system, addressing issues identified during Phase I. Based on the experience gained in phase I, we will develop a completely air cooled system eliminating the need for water-cooling. This will improve the reliability of the gyrotron and will further reduce the cost of the system. As a result of this project, we expect Bridge 12 to make available a compact, high-power, high-frequency, and tunable gyrotron, which has a variety of uses in biomedical areas beyond NMR spectroscopy such as in-vivo medical imaging and for diagnosis of cancer and possibly its treatment. PUBLIC HEALTH RELEVANCE: The proposed research is directed at designing and demonstrating a compact, cost-effective high- frequency, tunable 2nd-harmonic gyrotron for Dynamic Nuclear Polarization (DNP) enhanced solid-state Nuclear Magnetic Resonance (SSNMR) spectroscopy at 600 MHz. DNP has the capability to enhance the inherently small signal intensities observed in an NMR experiment by several orders of magnitude, and therefore dramatically increase the overall sensitivity of the method and reduce the acquisition time. This is of high interest for structural biology, pharmaceutical research and material science;areas that are of significant interest to research funded by the U.S. National Institutes of Health. The proposed system can be scaled to match SSNMR systems up to 800 MHz and can be installed without altering the layout of current NMR facilities. It is platform-nonspecific, enabling the upgrade (retro-fit) of existing SSNMR systems. This will enable the proliferation of solid-state DNP/NMR to a wider audience at a reasonable cost. The heart of the system will be a compact, tunable terahertz gyrotron source, which could also be used for in-vivo imaging for diagnosis of cancer and possibly its therapy.